Parthenin, a sesquiterpene lactone of Parthenium hysterophorus L. is a high toxicity clastogen

Ramos, Araceli Marcela; Rivero, Reinaldo; Visozo, Angel; Piloto, Janet; García, Arilia

doi:10.1016/s1383-5718(01)00321-7

Cited by 42 publications

(37 citation statements)

References 25 publications

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“…However, contrary to our negative results and those of Di Soto et al in bacteria, 2) other sesquiterpenes have given positive results: this is the case of the compound lactone lynchnopholide that was reported as a chromosome damaging agent in in vitro and in vivo assays, and was shown to be cytotoxic in vitro 11) ; another such case is that of parthenin which presented a strong capacity to induce micronuclei in vivo. 12) These divergent results suggest the relevance of the chemical structure in the biological effect of sesquiterpenes, and indicate as well the importance of using various test models to reach a valid conclusion. Concerning this last point, Morales et al compared the effect of 11 sesquiterpenoids in the Ames and the V79/HGPRT tests, and they found congruence in only four of them.…”

Section: Resultsmentioning

confidence: 99%

Clastogenicity of Beta-Caryophyllene in Mouse

Molina-Jasso

Álvarez-González

Madrigal-Bujaidar

2009

Biological & Pharmaceutical Bulletin

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Section: Resultsmentioning

confidence: 99%

Clastogenicity of Beta-Caryophyllene in Mouse

Molina-Jasso

Álvarez-González

Madrigal-Bujaidar

2009

Biological & Pharmaceutical Bulletin

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“…For example, Vasconcellos et al (2007) found that the compound, 15-deoxygoyazensolide, induces mutations in S. cerevisiae. Ramos et al, (2002) showed that parthenin, another antimalarial lactone, induces the formation of chromosomal aberrations and micronuclei in peripheral lymphocytes. This study evaluates the genotoxic, and cytotoxic effects of artesunate on mammalian DNA, by exposing human lymphocytes to this drug in vitro.…”

Section: Introductionmentioning

confidence: 99%

In vitro evaluation of the genotoxic and cytotoxic effects of artesunate, an antimalarial drug, in human lymphocytes

Mota

Cardoso

Gomes

et al. 2011

Environ and Mol Mutagen

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Artesunate is one of the main antimalarial drugs used in several countries. It is a semisynthetic compound derived from artemisinin, a substance extracted from the Chinese plant, Artemisia annua L. Despite the widespread use of artesunate as an antimalarial drug, there is a lack of data regarding its genotoxic effects in human lymphocytes. Therefore, in this study, we used the comet assay and micronucleus test to evaluate the possible genotoxic effects of artesunate in cultured human lymphocytes. In addition, cell death by necrosis and apoptosis was also assessed. Cells exposed to different concentrations of artesunate showed a significant concentration-dependent increase (P < 0.05) in DNA damage index and micronuclei frequency. A significant increase in the frequency of apoptotic and necrotic cells was also observed. Our results showed that artesunate is a genotoxic and cytotoxic compound in cultured human lymphocytes.

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“…Microgametogenesis and exflagellation occur within 15 min of entering the mosquito midgut and involve three rounds of DNA replication (1n to 8n) and partitioning of nuclear material to flagella. This phenomenon suggests that exflagellation may be vulnerable to the hypothesized effects of parthenin because parthenin has been shown to damage DNA in quickly replicating cancerous cell lines (18,(22)(23)(24), and artemisinin has been shown to have similar effects (43). To control for total numbers of male gametocytes present in each sample, we tested the various concentrations of parthenin against two different gametocyte densities: medium (0.5%) and high (1%).…”

Section: Resultsmentioning

confidence: 99%

“…Further studies on parthenin have revealed that it has a wide array of potentially useful biological effects and that it has shown activity as a potential herbicide (10,12,13), pesticide (14,15), antiparasitic (16,17), and anticancer compound (18)(19)(20)(21). Parthenin may act through a variety of mechanisms, including directly damaging DNA, inhibiting oxidative phosphorylation, inducing formation of nitric oxide, and promoting apoptotic signaling (18,19,(22)(23)(24)(25). General cytotoxicity of parthenin remains a concern, but its activity varies greatly among different cell lines, as illustrated by 50% inhibitory concentrations (IC 50 s) of 0.061 M and 594 M against Jurkat cells and HeLa cells, respectively (26).…”

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confidence: 99%

The Nonartemisinin Sesquiterpene Lactones Parthenin and Parthenolide Block Plasmodium falciparum Sexual Stage Transmission

Balaich

Mathias

Torto

et al. 2016

Antimicrob Agents Chemother

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f Parthenin and parthenolide are natural products that are closely related in structure to artemisinin, which is also a sesquiterpene lactone (SQL) and one of the most important antimalarial drugs available. Parthenin, like artemisinin, has an effect on Plasmodium blood stage development. We extended the evaluation of parthenin as a potential therapeutic for the transmissible stages of Plasmodium falciparum as it transitions between human and mosquito, with the aim of gaining potential mechanistic insight into the inhibitory activity of this compound. We posited that if parthenin targets different biological pathways in the parasite, this in turn could pave the way for the development of druggable compounds that could prevent the spread of artemisinin-resistant parasites. We examined parthenin's effect on male gamete activation and the ookinete-to-oocyst transition in the mosquito as well as on stage V gametocytes that are present in peripheral blood. Parthenin arrested parasite development for each of the stages tested. The broad inhibitory properties of parthenin on the evaluated parasite stages may suggest different mechanisms of action between parthenin and artemisinin. Parthenin's cytotoxicity notwithstanding, its demonstrated activity in this study suggests that structurally related SQLs with a better safety profile deserve further exploration. We used our battery of assays to test parthenolide, which has a more compelling safety profile. Parthenolide demonstrated activity nearly identical to that of parthenin against P. falciparum, highlighting its potential as a possible transmission-blocking drug scaffold. We discuss the context of the evidence with respect to the next steps toward expanding the current antimalarial arsenal.A n estimated 198 million cases of malaria and 584,000 deaths, mostly among young children, were reported worldwide in 2013 (1). However, as a result of concerted control efforts since 2000, including antimalarial drugs, mortality has declined by 47%, resulting in an estimated 4.3 million lives saved (1). Artemisinin, delivered with a partnered drug, is one of the fastest acting antimalarial therapies available (2, 3). However, antimalarial resistance in Plasmodium falciparum has been described recently in Southeast Asia (4). This discovery emphasizes the need for novel compounds that are effective against resistant strains, presumably because they act on the parasite differently from artemisinin. Artemisinin was originally isolated from Artemisia annua, or sweet wormwood, a member of the Asteraceae family. We hypothesized that natural product compounds derived from related family members might retain potent activities against Plasmodium while targeting different biological pathways.Parthenin is a sesquiterpene lactone (SQL) derived from Parthenium hysterophorus, which is an invasive, flowering annual weed in the Asteraceae family; it grows to 2 m in height, with small white flowers, and has spread throughout much of the world (5). P. hysterophorus causes millions of dollars in damag...

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Parthenin, a sesquiterpene lactone of Parthenium hysterophorus L. is a high toxicity clastogen

Cited by 42 publications

References 25 publications

Clastogenicity of Beta-Caryophyllene in Mouse

Clastogenicity of Beta-Caryophyllene in Mouse

In vitro evaluation of the genotoxic and cytotoxic effects of artesunate, an antimalarial drug, in human lymphocytes

The Nonartemisinin Sesquiterpene Lactones Parthenin and Parthenolide Block Plasmodium falciparum Sexual Stage Transmission

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